TY - JOUR AU - Kennedy, Oliver John AU - Kicinski, Michal AU - Valpione, Sara AU - Gandini, Sara AU - Suciu, Stefan AU - Blank, Christian U AU - Long, Georgina V AU - Atkinson, Victoria G AU - Dalle, Stéphane AU - Haydon, Andrew M AU - Meshcheryakov, Andrey AU - Khattak, Adnan AU - Carlino, Matteo S AU - Sandhu, Shahneen AU - Larkin, James AU - Puig, Susana AU - Ascierto, Paolo A AU - Rutkowski, Piotr AU - Schadendorf, Dirk AU - Boers-Sonderen, Marye AU - Di Giacomo, Anna Maria AU - van den Eertwegh, Alfonsus J M AU - Grob, Jean-Jacques AU - Gutzmer, Ralf AU - Jamal, Rahima AU - van Akkooi, Alexander C J AU - Robert, Caroline AU - Eggermont, Alexander M M AU - Lorigan, Paul AU - Mandala, Mario TI - Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma. JO - European journal of cancer VL - 189 SN - 0014-2964 CY - Amsterdam [u.a.] PB - Elsevier M1 - DKFZ-2023-01106 SP - 112900 PY - 2023 N1 - 2023 Aug;189:112900 AB - Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial.Patients with resected high-risk stage IIIA, IIIB, or IIIC melanoma received 200 mg of pembrolizumab (n = 514) or placebo (n = 505) every 3 weeks for twelve months. Pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) at approximately 42 months median follow-up (Eggermont et al., TLO, 2021). Multivariable Cox regression was used to estimate associations of metformin with RFS and DMFS. Interaction terms were used to model effect modification by treatment and BRAF mutation.Fifty-four patients (0.5 KW - BRAF (Other) KW - Immunomodulation (Other) KW - Immunotherapy (Other) KW - Melanoma (Other) KW - Metformin (Other) LB - PUB:(DE-HGF)16 C6 - pmid:37277264 DO - DOI:10.1016/j.ejca.2023.04.016 UR - https://inrepo02.dkfz.de/record/276423 ER -